The treatment of disease through cell encapsulation is based on entrapping hormone or enzyme producing cells within a matrix that is permeable to cell products and nutrients, while protecting the cells from the immune system. The most commonly studied capsule is the APA capsule consisting of alginate-poly-L-lysine-alginate layers. This three layer capsule consists of a calcium cross-linked alginate hydrogel core surrounded by poly-L-lysine (PLL), a polycation, and an outer coating of polyanion (alginate). The PLL layer strengthens the capsule and controls the permeability while the outer layer of polyanion is designed to reduce the high charge density of the PLL and to reduce immune reaction to the capsule itself.
These capsules pose many challenges in terms of strength and biocompatibility. To improve strength, the outer alginate layer has been replaced with reactive polymers such as poly(methyl vinyl ether-alt-maleic anhydride) (PMM50) and poly(4,4-dimethyl-2-vinyl-2-oxazoline-5-one-co-methacrylic acid), which are capable of forming covalent cross-links with the surface bound Pa. However, the presence of high charge density PLL near the capsule surface remains a potential problem for host-compatibility. In addition, high charge density polycations are quite cytotoxic and can be detrimental to the encapsulated cells.
There have recently been attempts to improve the biocompatibility of polycations reducing the positive charge density. One approach has been to dilute or mask the positive charges of PLL by grafting PLL with poly-ethylene glycol (PEG). While this indeed reduces cytotoxicity, the PEG chains can interfere with the coating process, and regions of PLL-g-PEG may retain high local charge density. Copolymers have been developed in which the cationic monomers have been diluted using neutral hydroxy-functional comonomers, forming synthetic analogs to chitosan, a natural amine-functional polysaccharide. These charge-reduced polyamines also experience lower electrostatic complexation efficiency and a reduced ability to form covalently cross-linked networks.
It would be desirable, thus, to provide a novel polymer system that overcomes or minimizes at least one disadvantage of prior such systems.